FDA

Modeyso approved for H3 K27M-mutant diffuse midline glioma

August 13, 2025

Brand name: Modeyso

Generic name: dordaviprone

Manufacturer: Jazz Pharmaceuticals

Approval date: August 6, 2025

FDA granted accelerated approval to Modeyso (dordaviprone), a protease activator, for the treatment of adult and pediatric patients ≥1 year of age with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.

Efficacy

The efficacy of Modeyso was evaluated in adult and pediatric patients with glioma across five open-label, non-randomized clinical trials conducted in the U.S. (ONC006 [NCT02525692], ONC013 [NCT03295396], ONC014 [NCT03416530], ONC016 [NCT05392374], and ONC018 [NCT03134131]). Pre-specified criteria were defined to establish an integrated efficacy population; eligible patients were required to have received single-agent Modeyso, have diffuse midline glioma harboring an H3 K27M mutation with progressive and measurable disease per Response Assessment in Neuro-Oncology-High Grade Glioma (RANO-HGG) criteria, be ≥90 days post-radiation therapy, have adequate washout from prior anticancer therapies, have a Karnofsky Performance Status/Lansky Performance Status (KPS/LPS) score ≥60, and have stable or decreasing corticosteroid use. Patients with diffuse intrinsic pontine glioma (DIPG), primary spinal tumors, atypical histologies, or CSF dissemination were excluded. Patients received weight-based dosing of Modeyso until disease progression or unacceptable toxicity.

The integrated efficacy population included 50 patients who met these criteria. The major efficacy outcome measure was overall response rate (ORR) assessed by blinded independent central review (BICR) according to RANO 2.0 criteria. Additional efficacy outcome measures were BICR-assessed ORR according to RANO-HGG criteria and Response Assessment in Neuro-Oncology-Low Grade Glioma (RANO-LGG) criteria, duration of response, and time to response.

The overall response rate was 22% (95% confidence interval [CI], 12-36), with 16% of patients experiencing a partial response and 6% experiencing a minor response.

Median duration of response was 10.3 months (95% CI, 7.3-15.2). Among responders (n=11), 73% maintained a response for at least 6 months and 22% maintained a response for at least 12 months. Median time to response was 3.6 months (range, 1.6-15.6).

Safety

The most common (≥20%) adverse reactions in the clinical trials were fatigue, headache, vomiting, nausea, and musculoskeletal pain. The most common (≥2%) Grade 3 or 4 lab abnormalities were decreased lymphocytes, decreased calcium, and increased ALT.

Sources:

Modeyso (dordaviprone) [package insert]. Jazz Pharmaceuticals. https://pp.jazzpharma.com/pi/modeyso.en.USPI.pdf Revised August 2025. Accessed August 12, 2025.

Jazz Pharmaceuticals announces US FDA approval of Modeyso™ (dordaviprone) as the first and only treatment for recurrent H3 K27M-mutant diffuse midline glioma. [News release]. 2025. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-us-fda-approval-modeysotm